Strategy to Estimate Sample Sizes to Justify the Association between MMP1 SNP and Osteoarthritis.

Background: the impact of knee osteoarthritis (OA) poses a formidable challenge to older adults. Studies have reported that genetic factors, such as MMP1, are one of important risk factors for knee OA. Although the relationship between the genetic polymorphism of MMP1 rs1799750 and the risk of knee OA has been explored, conclusions have been nonunanimous and pending due to research sample sizes, one of determinants in studying genetic polymorphisms associated with disease. Objective: to establish a model to assess whether the genetic polymorphism of MMP1 rs1799750 is associated with knee OA based on an estimation of sample sizes. Methods: samples were collected from a case−control and meta-analysis study. In the case−control study, patients who underwent knee X-ray examinations based on the Kellgren−Lawrence Grading System (KL) as diagnostic criteria were recruited at the Health Examination Center of the Tri-Service General Hospital from 2015 to 2019. Gene sequencing was conducted using iPLEX Gold. Those with unsuccessful gene sequencing were excluded. Finally, there were 569 patients in the knee OA group (KL ≥ 2) and 534 participants in the control group (KL < 2). In the meta-analysis, we used the databases PubMed, EMBASE, and Cochrane to search for studies on the relationship between MMP1 rs1799750 and knee OA. Next, we adopted the trial sequential analysis (TSA) method to assess whether sample sizes were sufficient or not to determine the risk of the genetic polymorphism of MMP1 rs1799750 on knee OA in Caucasians and Asians. Results: in Caucasians, the MMP1 rs1799750 was not significantly associated with knee OA with an odds ratios (OR) of 1.10 (95% confidence interval, CI: 0.45−2.68). Some extra 8559 samples were needed to conclude this relationship in Caucasians by the TSA model. In Asians, neither our case−control study results (n = 1103) nor a combination of samples from the case−control and meta-analysis results showed an association between MMP1 rs1799750 and knee OA. The OR (95% CI) was 1.10 (0.81−1.49) in a combination of Asian samples. Some extra 5517 samples were needed to justify this relationship in Asians by the TSA model. Conclusions: this research shows that an extra 8559 and 5517 samples are needed in Caucasians and Asians, respectively, in order to justify the association between MMP1 rs1799750 and knee OA.

The Decisive Case-Control Study Elaborates the Null Association between ADAMTS5 rs226794 and Osteoarthritis in Asians: A Case-Control Study and Meta-Analysis.

BACKGROUND: Osteoarthritis is an important health issue for the elderly. Many studies indicate that genetics is an important risk factor for osteoarthritis, and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS5) is one gene that is most frequently implicated. Many recent studies have examined the relationship between a polymorphism in the ADAMTS5 gene (rs226794) and the risk for developing osteoarthritis without definitive results. OBJECTIVE: In this case-control study, we examined the correlation between the ADAMTS5 gene polymorphism, rs226794, and knee osteoarthritis. We used a meta-analysis and trial sequential analysis to determine whether ADAMTS5 rs226794 expression increases susceptibility to osteoarthritis. METHODS: This study consisted of two parts: a case-control study and a meta-analysis. The case-control study included subjects who underwent knee radiography at the Health Examination Center of the Tri Service General Hospital from 2015 to 2019. The Kellgren-Lawrence (KL) grading system was used as diagnostic criteria. Patients with unsuccessful gene sequencing were excluded. There were 606 subjects in the knee osteoarthritis group (KL ≥ 2) and 564 in the control group (KL < 2). Gene sequencing was performed using iPLEX Gold to determine the association between the gene polymorphism of ADAMTS5 rs226794 and knee osteoarthritis. For the meta-analysis, databases such as PubMed, Embase, and Cochrane were queried to identify studies that examined the relationship between ADAMTS5 rs226794 and osteoarthritis. Next, the findings of the meta-analysis were incorporated with the results of the case-control study and samples from the published studies to estimate the association between the genetic polymorphism and osteoarthritis using an odds ratio and a 95% confidence interval. RESULTS: We found a non-significant association between the G allele and knee OA (crude-OR: 0.93 (95% CI: 0.79-1.10) and adjusted-OR: 1.02 (95% CI: 0.76-1.36) in the allele model) in the present study, and the analysis of other genetic models revealed a similar trend. After including five published studies and our case-control study, the results with 2866 Asians indicated a conclusively null association between ADAMTS5 rs226794 and knee OA) OR: 1.09 (95% CI: 0.93-1.26). The results for Caucasians also revealed a null association (OR: 1.21 (95% CI: 0.81-1.82)). CONCLUSIONS: This study indicates that the gene polymorphism, ADAMTS5 rs226794, is not significantly associated with knee osteoarthritis. Additionally, assuming that the cumulative sample size in the allele model is sufficient, we confirmed that the G allele is not a risk factor for osteoarthritis. This study integrated all available evidence to arrive at this conclusion, and it suggests that no additional studies are necessary.